This research project proposes a coordinated, multidisciplinary investigation of the possible relationship between the actions of drugs on deprivation-induced fluid consumption by rats and the demonstrated ability of these drugs to produce physical dependence in man. By examining appropriate behavioral, biochemical and physiological parameters associated with this effect, an attempt will be made to uncover the mechanism(s) involved in these processes. Studies will be made of acute and chronic dosage regimens, using a variety of behavioral test systems including operant-licking and continuous avoidance to determine the specificity of this effect. Attempts will be made to pharmacologically evaluate the neurobiochemical pathways involved. Drug-drug interactions will be used to study antagonistic and synergistic phenomena, and depletors of brain biogenic amines will be used to confirm possible roles for biogenic amines in these phenomena. Through these efforts it should be possible to develop better animal models for studying the problem of drug dependence and possibly for designing better therapeutic approaches to its treatment.